The action of anaesthetics and high pressure on neuronal discharge patterns

1. The membrane actions of both anaesthetics and high pressure have been studied in rat hippocampal slices in experiments where either field potential (orthodromic or antidromic) responses from the CA1 region are recorded or intracellular measurements in CA1 neurones are made. 2. It is clear that anaesthetics have multiple post-synaptic actions in CA1 pyramidal neurones. For example, the amplitude of antidromic field potential responses are depressed (e.g. 2.5% enflurane) or increased (20 mM ketamine) or recruitment of a second population spike occurs (2.5% halothane). 3. In separate intracellular experiments anaesthetics have been shown to hyperpolarize [e.g. inhalations (2.5%), or methohexitone, 50-100 microM), or depolarize (ketamine, > or = 20 microM), CA1 pyramidal neurones decreasing or increasing respectively the responses to weak depolarizing synaptic input, or direct stimulation. 4. In the case of some anaesthetics (inhalation agents or ketamine), the accommodation of action potential discharge is also decreased, this being accompanied by a reduction in the amplitude of the associated slow after hyperpolarization (AHP). Consequently many neurones fire repetitively in response to long lasting, strong depolarizing inputs. Sub-classes of K+ channel such as the M (channel closed by muscarinic agonists) and the SK (Ca(2+)-dependent K+ channel of small conductance) type are currently believed to control the accommodation of spike discharge and the AHP. Consistent with this idea is the finding that in voltage-clamp experiments enflurane decreased reversibly the M current. 5. Methohexitone (50 microM) does not block the accommodation of action potential discharge but interestingly induces a long lasting depolarization and action potential bursting. 6. In comparison, high pressure (51-101 ATA) can induce a second population spike in antidromic field potential recordings, indicative also of a post-synaptic action. 7. There is no apparent change in the resting membrane potential or input resistance of CA1 neurones at high pressure, however 51 or 101 ATA produced a reduction in the accommodation of action potential discharge and the associated AHP leading to repetitive discharge in response to strong (0.7 nA) depolarizing currents. 8. In a few neurones spontaneous depolarizations and action potential discharge also occurred during compression between 51-101 ATA. 9. Our working hypothesis is that certain subclasses of neuronal K+ channel represent interesting targets for both anaesthetic and high pressure action.